U.S. Pat. No. 5,089,273, describes novel compositions of matter extracted from the tropical marine invertebrate, Ecteinascidia turbinata, and designated therein as ecteinascidins 729, 743, 745, 759A, 759B and 770. These compounds are useful as antibacterial and/or antitumor agents in mammals. Ecteinascidin 743 is undergoing clinical trials as an antitumour agent.

The limited availability of natural material has resulted in the search for alternative synthetic methods being sought for the natural compounds and related analogs.
A synthetic process for producing ecteinascidin compounds is described in U.S. Pat. No. 5,721,362. The claimed method involves many steps, there being 38 Examples each describing one or more steps in the synthetic sequence to arrive at ecteinascidin 743.
Shorter synthetic processes for producing Ecteinascidin 743 are described in WO 0069862 and WO 0187895 and involve the use of cyanosafracin B as starting material.
However, there is still a need to provide synthetic routes to other ecteinascidins, in particular to provide more economic paths to the known antitumour agents such as ET-729, as well as permitting the preparation of new compounds.
Synthetic ecteinascidin compounds are known from various earlier PCT filings, including for example WO 0018233, WO 0177115, WO 0187894, WO 0187895, WO 99 51238, and WO 9846080. All of these patent specifications are specifically incorporated by reference, especially for the guidance they give in the design and synthesis of ecteinascidin compounds. In particular, they reveal structure-activity relationships which may be applied to the compounds of the present invention. See also J. Am. Chem. Soc, 1996, vol. 118, no. 38, pages 9017-9023 for ecteinascidin compounds. The synthetic compounds and the natural ecteinascidins have a fused ring system:

In many ecteinascidins, there is a 1,4 bridge across the fused ring system. With the natural ecteinascidins, the 1,4 bridge is sometimes a 1,4-spiroamine bridge, as for instance in ecteinascidin 729, 736 or 743.